TOFACITINIB IN PSORIATIC ARTHRITIS -WELL TOLERATED DRUG - REAL LIFE EXPERIENCE

BackgroundTofacitinib a small molecule JAK- inhibitors has been approved for use in psoriatic arthritis (PSA) since 2017 while it has shown to be effective in the clinical trials real life data is sparse.With increase in use there has been growing concern about the safety profiles and adverse events which makes it all the more important to have real life data.ObjectivesTo review patient records who were treated with tofacitinib for psoriatic arthritis and to assess the tolerance and continuation rate and also assess the occurrence of adverse events like infections, coronary artery disease.MethodsAll PSA patients who were prescribed tofacitinib from JAN-2021 to JUNE 2022 with minimum of 6 months followup were included for analysis. Demographics, weight recordings, lab parameters and occurence of adverse events were noted.ResultsThere were a total of 71 patients who were prescribed tofacitinib out of which 46 are continuing and 25 have stopped during this period. The mean age was 47.25 (10.9)yrs the mean disease duration was 4.182 (4.474)yrs The reason for stopping tofacitinib was better(52%) followed inefficacy(24%), and miscellaneous(24%)reasons..When analysing before and after tofacitninb one thing whihc was striking is the significant weight gain among patients with minimum of 3.52(3.06) kg weight gain and this weight gain was consistent even in stopped patients.in comparing the lab parameters before and after tofacitininb there was a significant redcution in CRP,ESR,PLATELET COUNT Table 1 and a minimal but insginificant rise in liver enzymes within the physiological range.When compared to before and after tofacitinib there was increased occurence of fatigue(18.3%), minor infections(11.2%), Gastrointerstinal adverse events (11.2%), alopecia (11.2%), Itching(10.4%), headache(9.8%), UTI(5.6%), cough (4.2%), transaminitis(2.8%), covid(1.7%), zoster(1.4%) and CAD(1.4%).ConclusionTofacitinib in psoriatic arthritis is well tolerated with significant reduction in the inflammatory markers and weight gain but serious adverse events in lesser percentage eventhough it leads to significant weight gain.Table 1.PARAMTERSBeforeAfterP valueWeight70.15 (14.19)72.31 (14.24)0.000249ESR45.29 (28.26)35.23 (28.33)0.037CRP21.56 (16.38)10.72 (11.98)<.0001PLATELET COUNT332.92 (88.77)307.09 (88.18)0.0046SGOT30.33 (9.99)35.69 (19.92)0.125SGPT22.57 (12.96)27.98 (20.17)0.116Reference[1]Ly K, Beck KM, Smith MP, Orbai A-M, Liao W. Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives. Psoriasis (Auckl) [Internet]. 2019;9:97–107. Available from: https://doi.org/10.2147/PTT.S161453Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Impact of Early Termination of Lockdown and Maintaining Social Distancing: COVID-19

A novel corona-virus named COVID-19 has spread rapidly and has caused a global outbreak of respiratory illness. It has been confirmed that the bats are the source host of SARS, and camels act as a source for MERS. However, the source host of the COVID-19 remains unknown. All three kinds of pneumonia show human-to-human transmissions. Among which, COVID-19 shows a longer incubation period. The routes for the human to human transmission are common, respiratory droplets, contact, and aerosol. In which, the new form is Aerosol transmission. In which, integration of the air with droplets will occur during transmission that leads to the formation of Droplet Nucleus. It can lead to infection after inhalation. Because of this, the virus has already spread to South Korea, Japan, Iran, Italy, and other countries. The objective of this chapter is to address the impact and list the suggestion to handle COVID-19 safely. The methodology followed in drafting this chapter is to provide answers to the following questions: Q1: The clinical manifestation of COVID-19? Q2: How to prevent the transmission of this disease and protect themselves? Q3: The outcome of COVID-19 pneumonia. Q4: How to diagnose COVID-19? Q5: The effects of COVID-19 pneumonia on pregnancy: Q6: Coronavirus pneumonia in children. Q7: The response strategies against the COVID-19 in China. Q8: Therapeutic Strategy for COVID-19. Q9: Consequences of COVID-19 in Human Daily Life. Q10: How to deal with the novel Coronavirus disease calmly? Q11: The COVID-19 prevention among students. Q12: Plan to return to the campus. Q13: Home-based self-care in climacteric women Q14: Strategies to climacteric women's psychological problems during COVID-19 pandemic. The outcome of the present research is to provide suggestions to the humankind towards handling the epidemic safely. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

From virtual to hybrid: attendees' ideas for virtual conference improvements and future conferences

Background: COVID-19 forced conferences online, but with easing travel restrictions amid ongoing uncertainty, organisers have begun planning for hybrid (virtual and in-person) formats. Understanding attendees' needs and ideas will improve conference planning. Aim(s): To explore attendees' perspectives on virtual conference improvements and their ideas for the in-person and virtual components of future hybrid conferences. Method(s): An online survey was distributed to 16,888 attendees of an international virtual conference. Result(s): 823 (4.9%) surveys were completed. Frequently mentioned needs were technical improvements (n=77), greater interactivity between delegates (n=54) and fewer simultaneous sessions (n=38). 56% of respondents would prefer a hybrid format in future with virtual sessions held throughout the year and an in-person conference;33% prefer in-person and 11% prefer virtual formats alone. For in-person activity, respondents would prioritize clinical skills workshops (n=132), replication of previous traditional conference presentation formats (n=79) and debates (n=45). For virtual activity, respondents would prioritize having the virtual conference format similar to as conducted in 2021, (n=118), clinical case discussions (n=95) and topic review sessions (n=49). Conclusion(s): Attendees suggest technical improvements and greater interactivity as virtual conference improvements. Future conferences are preferred in a hybrid format, with a virtual component similar to the previous virtual congress and an in-person component including live clinical skills workshops.

Targeting non-structural proteins and 3CL(pro) in SARS-CoV-2 virus using phytochemicals from medicinal plants- In-silico approach

In the present study, the main protease 3CL(pro) and non-structural protein (NSP-12 with co-factors 7 and 8) trimer complex are used to study the protein-drug interactions with the phytochemicals from Ocimum Sanctum, Tinospora Cordifolia, Glycyrrhiza Glabra, and Azadirachta Indica. Which can give insight to be used as potent antiviral drugs against SARS-CoV-2. Twenty phytochemicals, five from each plant species, known for their wide range of biological activities were chosen from the literature. The in-silico study was carried out using virtual screening tools and the top five, which showed the least binding energies, were selected. Molecular docking tools revealed that gedunin and epoxy azadiradione proved to be excellent inhibitors for 3CL(pro) and so did Tinosporide for nonstructural-protein complex. Further, the best-hit phytochemicals with respect to structure similarities with FDA drugs and investigatory drugs, were considered for comparative study. Molecular docking was done to check the drug-protein interactions and to check the inhibitory responses of these drugs against the viral protein. The analyses showed that the phytochemicals had similar responses on the protein complex but with exceptionally higher inhibitory responses hence which may be taken for further clinical study.

Pulmonary Image Analysis with Computer Vision Using Binary Classification Method for COVID-19 Detection

The advent of COVID-19 raised a terrorizing situation across the globe. The virus is spreading at an exponential rate since its beginning which was first identified in the Wuhan province, China, in the year 2019 in the month of December. The virus belongs to a family similar to that of the severe acute respiratory syndrome (SARS) which was identified in the year 2002. It has a complex structure which makes it difficult for scientists to get the exact action and cure for the disease. The spread of the virus takes place only by body fluids (saliva, mucosa, etc.). Various research organizations, pharmaceuticals, and institutes are working on the production of testing kits and vaccinations, though some of them are already being produced in the market. The testing kits produced are less in numbers due to the lack of resources and knowledge gathered to detect and fight the virus properly because of which not everyone is getting the chance to get themselves checked. Computer tomography and X-rays of the pulmonary region along with various acquaintance and methods of AI deep learning give an effective alternative that can be employed. This stratagem can be applied using a dataset consisting of images of various X-rays and CT-scans which are of patients who are COVID-19 positive and also of healthy people. This diagnosing tool uses the binomial classification method. The accuracy and the working of the tool primarily depend on accessible information and data for better processing. Post testing of the tool shows us that it is flexible and accurate to use. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Covid-19 Infection in Hematological Malignancies: Registry Data from India

Background: The impact of COVID-19 pandemic has been highly heterogeneous across the globe and different regions within the country. The differences in the outcome of these patients is related to their demographic profile, genetics, socio-economic conditions, and government health policies. Prior to the COVID-19 pandemic, the Healthcare Access and Quality (HAQ) Index for hematological malignancies (HAQ index <30) in a low-middle socio-demographic index(SDI) country like India was less than the mean HAQ index for all other diseases (HAQ index 41) with a significant regional disparity.(1)Several national and international registries from high socio-demographic Index (SDI) countries have reported worse short-term outcomes of coronavirus disease (COVID-19) in patients with hematologic as compared to other solid cancers. The outcomes of COVID-19 in patients with hematologic malignancies from a low-middle SDI country are yet unknown. The COVID-19 Hematologic Cancer registry of India reports these outcomes from India. Methods: Ten tertiary referral hospitals across India reported the demographic, clinical, laboratory, treatment, and outcomes of COVID-19 infection in patients with hematological malignancies. The registry was retrospective from March 21, 2020, and prospective from November 1, 2020, till March 20, 2021. Risk factors associated with severity and mortality were evaluated using the penalised logistic regression and Cox proportional hazards model. Findings: Data from 565 patients was included in this study. Among these, 429 (76%) patients were hospitalized, 186 (33%) patients had moderate/severe COVID-19.There were 116 (20.5%) non-survivors at a mean follow up of 147 (95% CI : 142-153) days. Age >60 years (HR 2·55, 1·23 - 5·27), diagnosis of acute myeloid leukemia (HR 2·85, 1·58 - 5·13), interruption or alteration of anticancer therapy (HR 2·78, 1·65 - 4·68), and post hematopoietic cell transplant status (HR 3·68, 1·82 - 7·45) predicted mortality. In contrast, increasing age [20-40 years (OR 2·54, 1·32 - 4·90), 41-60 years (OR 3·51, 1·84 - 6·71), >60 years (OR 6·04, 3·01 - 12·10), comorbidities such as diabetes mellitus (OR 1·89, 1·18 - 3·04), hypertension (OR 1·94, 1·17 - 3·19), diagnosis of AML (OR 3·70, 2·06 - 6·67), indolent non-hodgkin lymphoma (OR 3·20, 1·68 - 6·09), multiple myeloma (OR 2·88, 1·64 - 5·05), malignancy not being in remission (OR 1·71, 1·12 - 2·60)were significantly associated with severe COVID-19 on univariate analysis. Of these, only increasing age [20-40 years (OR 2·60 (1·31 - 5·15), 40-60 years (OR 3·44, 1.60 - 7·41), more than 60 years (OR 5·70, 2·43 - 13·35)], AML (OR 2·73, 1·45 - 5·12), and malignancy not being in remission (OR 1·85, 1·18 - 2·89) were significantly associated with severe COVID-19 on multivariable analysis Conclusion: The overall mortality from COVID-19 infection of the entire cohort was 20.5%;the mortality was 46.2% in patients who had moderate to severe disease COVID-19 illness. Similar to previous studies, age, diagnosis of acute myeloid leukemia and a post stem cell transplant status was associated with mortality. In addition, interruption or de-escalation of anticancer therapy during Covid-19 infection was identified as an important factor associated with higher mortality on follow up in the current study. References 1. Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016. Lancet (London, England)2018;391(10136): 2236-71.Lee AJX, Purshouse K. COVID-19 and cancer registries: learning from the first peak of the SARS-CoV-2 pandemic. Br J Cancer 2021;124(11): 1777-84. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial.

OBJECTIVE: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma. DESIGN: Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease. SETTING: 39 public and private hospitals across India during the study period from 22 April to 14 July 2020. PARTICIPANTS: Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed. PRIMARY OUTCOME MEASURE: Factors associated with all-cause mortality at 28 days after enrolment. RESULTS: The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3-7) and non-survivors (4 days; IQR 3-6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p<0.001) in non-survivors and increased further on day 3. On multivariable Fine and Gray model, severity of illness (subdistribution HR 1.22, 95% CI 1.11 to 1.35, p<0.001), PaO2/FiO2 ratio <100 (3.47, 1.64-7.37, p=0.001), neutrophil lymphocyte ratio >10 (9.97, 3.65-27.13, p<0.001), D-dimer >1.0 mg/L (2.50, 1.14-5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44-4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60-5.45, p=0.001) were significantly associated with death. CONCLUSION: In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death. TRIAL REGISTRATION NUMBER: CTRI/2020/04/024775.

Evaluation of Gamma glutamyl-transferase (GGT) levels in COVID-19: A retrospective analysis in tertiary care centre

Many recent studies have reported that patients infected with novel coronavirus 2019 or SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) might have a liver injury. However, few studies have focussed on the levels of Gamma glutamyl-transferase (GGT) alone and the variations associated with it. We retrospectively analysed the GGT levels of 476 admitted patients with confirmed COVID-19 in a tertiary care centre, PGIMER (Post Graduate Institute of Medical Education and Research), Chandigarh. Out of the total 476 COVID-19 patients studied, 35% had elevated GGT levels. ICU care was required for 51.19% (P <0.0001) of these patients and their hospital stay was of longer duration as compared to the patients with normal GGT levels. The incidence of GGT elevation was found to be more pronounced in males and elderly patients. The male population displayed higher GGT levels with 52% having raised levels compared to females where only 21.6% had elevated GGT levels. Although the number of COVID-19 cases was majorly from young age groups, the elevation in GGT levels has been reported more in elderly patients. GGT levels can therefore serve as a predictor for the extent of liver injury and severity in COVID-19 patients.

Statistical analysis on novel corona virus: COVID-19

A novel coronavirus, 2019nCoV is identified as the root cause for such a deadly outbreak causing respiratory illness. Due to its widespread impact on the global community, stringent measures were implemented to reduce the effect of the outbreak;self-precautionary measures like using face-masks, hand hygiene, and self-quarantine;environmental measures were insisted to follow and also surface cleaning and community measures to prevent the widespread. The pandemic evolved in China towards the end of 2019 and COVID 19 started to spread all over the globe like a typical wildfire capturing over 190 countries. It grows in a human body with common symptoms like common cold leading to respiratory problems and at times even death. The virus grows exponentially. So, based on the symptoms and the activity of the virus various measures have been implemented. The death rate peaked in the USA and Iran at the end of March and due to comorbidities and many medications has helped in cutting down the numbers. The rate of spread did not shoot up in countries like India due to preventive and cautious care and also due to reduced human contact from the countries with incidence or spread of the vector to other countries.

UVA radiation could be a significant contributor to sunlight inactivation of SARS-CoV-2 (preprint)

Past experiments demonstrated SARS-CoV-2 inactivation by simulated sunlight; models have considered exclusively mechanisms involving UVB acting directly on RNA. However, UVA inactivation has been demonstrated for other enveloped RNA viruses, through indirect mechanisms involving the suspension medium. We propose a model combining UVB and UVA inactivation for SARS-CoV-2, which improves predictions by accounting for effects associated with the medium. UVA sensitivities deduced for SARS-CoV-2 are consistent with data for SARS-CoV-1 under UVA only. This analysis calls for experiments to separately assess effects of UVA and UVB in different media, and for including UVA in inactivation models. Key words: SARS-CoV-2, COVID-19, environmental persistence, sunlight, UVA, UVB, modeling, inactivation methods, photobiology

Analysis of SARS-CoV-2 genomes from across Africa reveals potentially clinically relevant mutations. (preprint)

SARS-CoV-2 is a betacoronavirus, the etiologic agent of the novel Coronavirus disease 2019 (COVID-19). In December 2019, an outbreak of COVID-19 began in Wuhan province of the Hubei district in China and rapidly spread across the globe. On March 11th, 2020, the World Health Organization officially designated COVID-19 as a pandemic. Across the continents and specifically in Africa, all index cases were travel related. Thus, it is crucial to compare COVID-19 genome sequences from the African continent with sequences from COVID-19 hotspots (including China, Brazil, Italy, United State of America and the United Kingdom). To identify if there are distinguishing mutations in the African SARS-CoV-2 genomes compared to genomes from other countries, including disease hotspots, we conducted in silico analyses and comparisons. Complete African SARS-CoV-2 genomes deposited in GISAID and NCBI databases as of June 2020 were downloaded and aligned with genomes from Wuhan, China and other SARS-CoV-2 hotspots. Using phylogenetic analysis and amino acid sequence alignments of the spike and replicase (NSP12) proteins, we searched for possible targets for vaccine coverage or potential therapeutic agents. Our results showed a similarity between the African SARS-CoV-2 genomes and genomes in countries including China, Brazil, France, the United Kingdom, Italy, France and the United States of America. This study shows for the first time, an in-depth analysis of the SARS-CoV-2 landscape across Africa and will potentially provide insights into specific mutations to relevant proteins in the SARS-CoV-2 genomes in African populations.

A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates (preprint)

To contain the coronavirus disease 2019 (COVID-19) pandemic, a safe and effective vaccine against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is urgently needed in quantities sufficient to immunise large populations. In this study, we report the design, preclinical development, immunogenicity and anti-viral protective effect in rhesus macaques of the BNT162b2 vaccine candidate. BNT162b2 contains an LNP-formulated nucleoside-modified mRNA that encodes the spike glycoprotein captured in its prefusion conformation. After expression of the BNT162b2 coding sequence in cells, approximately 20% of the spike molecules are in the one-RBD up, two-RBD down state. Immunisation of mice with a single dose of BNT162b2 induced dose level-dependent increases in pseudovirus neutralisation titers. Prime-boost vaccination of rhesus macaques elicited authentic SARS-CoV-2 neutralising geometric mean titers 10.2 to 18.0 times that of a SARS-CoV-2 convalescent human serum panel. BNT162b2 generated strong TH1 type CD4+ and IFNy+ CD8+ T-cell responses in mice and rhesus macaques. The BNT162b2 vaccine candidate fully protected the lungs of immunised rhesus macaques from infectious SARS-CoV-2 challenge. BNT162b2 is currently being evaluated in a global, pivotal Phase 2/3 trial (NCT04368728).

In vitro study of BromAc on SARS-CoV-2 spike and envelope proteins shows synergy and disintegration at modest concentrations (preprint)

Objectives: SARS-CoV-2 infection is the cause of a worldwide pandemic, currently with limited therapeutic options. It is characterised by being highly contagious and nasal mucosa appears to be the primary site with subsequent spread to the lungs and elsewhere. BromAc (Bromelain & Acetylcysteine) has been described to disrupt glycoproteins by the synchronous breakage of glycosidic linkages and disulphide bonds. The spike protein of SARS-CoV-2 is an attractive target as it is essential for binding to the ACE2 receptor in host cells and is formed of glycoprotein and disulphide bridges for stabilisation. Hence, we sought to determine whether BromAc has activity on the spike and envelope protein specific to SARS-CoV-2 virus. Design: Gel electrophoresis analysis was carried out on recombinant spike and envelope proteins that were treated with a range of concentrations of single agents and BromAc. For UV analysis of disulfide bonds reduction, both spike and envelope protein were treated with Acetylcysteine with the determination of loss of disulfide bonds. Results: Recombinant spike and envelope SARS-CoV-2 protein were fragmented by BromAc whilst single agents had minimal effect. Spike and envelope proteins disulphide bonds were reduced by Acetylcysteine. Conclusion: BromAc disintegrates the spike and envelope protein from SARS-CoV-2 and may render it non-infective. In vitro tests on live virus have been encouraging and clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent.

Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial) (preprint)

ObjectivesConvalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. DesignOpen-label, parallel-arm, phase II, multicentre, randomized controlled trial. SettingThirty-nine public and private hospitals across India. ParticipantsHospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 [≤] 93% on room air). InterventionParticipants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome MeasureComposite of progression to severe disease (PaO2/FiO2< 100) or all-cause mortality at 28 days post-enrolment. ResultsBetween 22nd April to 14th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. InterpretationCP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19. Trial registrationThe trial was registered with Clinical Trial Registry of India (CTRI); CTRI/2020/04/024775.

Antibody binding to SARS-CoV-2 S glycoprotein correlates with, but does not predict neutralization (preprint)

Convalescent plasma from SARS-CoV-2 infected individuals and monoclonal antibodies were shown to potently neutralize viral and pseudoviral particles carrying the S glycoprotein. However, a non-negligent proportion of plasma samples from infected individuals as well as S-specific monoclonal antibodies were reported to be non-neutralizing despite efficient interaction with the S glycoprotein in different biochemical assays using soluble recombinant forms of S or when expressed at the cell surface. How neutralization relates to binding of S glycoprotein in the context of viral particles remains to be established. Here we developed a pseudovirus capture assay (VCA) to measure the capacity of plasma samples or antibodies immobilized on ELISA plates to bind to membrane-bound S glycoproteins from SARS-CoV-2 expressed at the surface of lentiviral particles. By performing VCA and neutralization assays we observed a strong correlation between these two parameters. However, while we found that plasma samples unable to capture viral particles did not neutralize, capture did not guarantee neutralization, indicating that the capacity of antibodies to bind to the S glycoprotein at the surface of viral particles is required but not sufficient to mediate neutralization. Altogether, our results highlights the importance of better understanding the inactivation of S by plasma and neutralizing antibodies.

Interaction of human ACE2 to membrane-bound SARS-CoV-1 and SARS-CoV-2 S glycoproteins (preprint)

A novel severe acute respiratory (SARS)-like coronavirus (SARS-CoV-2) is responsible for the current global coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The viral entry of SARS-CoV-2 depends on an interaction between the receptor binding domain of its trimeric Spike glycoprotein and the human angiotensin converting enzyme 2 (ACE2) receptor. A better understanding of the Spike/ACE2 interaction is still required to design anti-SARS-CoV-2 therapeutics. Here, we investigated the degree of cooperativity of ACE2 within both the SARS-CoV-2 and the closely related SARS-CoV-1 membrane-bound S glycoproteins. We show that there exist differential inter-protomer conformational transitions between both Spike trimers. Interestingly, the SARS-CoV-2 spike exhibits a positive cooperativity for monomeric soluble ACE2 binding when compared to the SARS-CoV-1 spike, which might have more structural restrains. Our findings can be of importance in the development of therapeutics that block the Spike/ACE2 interaction.

Mobile Fotonovelas Within a Text Message Outreach: An Innovative Tool to Build Health Literacy and Influence Behaviors in Response to the COVID-19 Pandemic.

With all 50 US states reporting cases of coronavirus disease (COVID-19), people around the country are adapting and stepping up to the challenges of the pandemic; however, they are also frightened, anxious, and confused about what they can do to avoid exposure to the disease. Usual habits have been interrupted as a result of the crisis, and consumers are open to suggestions and strategies to help them change long-standing attitudes and behaviors. In response, a novel and innovative mobile communication capability was developed to present health messages in English and Spanish with links to fotonovelas (visual stories) that are accessible, easy to understand across literacy levels, and compelling to a diverse audience. While SMS text message outreach has been used to build health literacy and provide social support, few studies have explored the benefits of SMS text messaging combined with visual stories to influence health behaviors and build knowledge and self-efficacy. In particular, this approach can be used to provide vital information, resources, empathy, and support to the most vulnerable populations. This also allows providers and health plans to quickly reach out to their patients and members without any additional resource demands at a time when the health care system is severely overburdened.